1. Field of Invention
The present invention relates generally to the maintenance of health and specifically to the lowering of systemic cholesterol levels in humans through the regular administration of a composition comprising oil seeds and nuts.
2. Background of the Invention
Certain abnormalities relative to cholesterol levels (e.g., high total cholesterol levels or high levels of low density lipoprotein (“LDL”), and/or low levels of high density lipoprotein (“HDL”)) are defined risk factors for cardiovascular, cerebrovascular, and peripheral vascular disease. Correction of these abnormalities decreases the risk of heart disease and stroke. Correction may be possible with dietary modifications but many times a medicine is needed. Presently available medicines are effective but they also carry the risk of sometimes significant side effects. Accordingly, in spite of the widespread incidence of cholesterol abnormalities, large numbers of people with these abnormalities do not take medicines.
Many studies have indicated that the consumption of many individual nuts and oil seeds are useful to correct cholesterol abnormalities. Nuts and oil seeds contain a variety of fats. Research has suggested that nuts and oil seed consumption in animals and humans has a beneficial effect for prevention of vascular or coronary artery disease. Five large prospective cohort studies (The Adventist Health Study, the Iowa Women Health Study, the Nurses' Health Study, the Physicians' Health Study, and the CARE Study) have all found an inverse relationship between nut consumption and risk of coronary heart disease. Hu and Stampfer, in their review of this subject, suggested that nuts should assume a more prominent place in the U.S. Department of Agriculture Food Guide Pyramid.
Many studies are available reporting the effect of an individual variety of nut. For example, Lovejoy et al. studied the effect of diets enriched in almonds on insulin action and serum lipids in normal adults and with type-2 diabetes. A beneficial effect was noted on serum lipids and the diet did not alter insulin sensitivity in healthy adults or glycemia in individuals with diabetes. Jenkins et al. studied the effect of almonds as a snack in hyperlipidemic subjects. A beneficial effect to lower LDL was noted in a dose response manner without any overt effects. Jambazian et al. reported improved plasma alpha-tocopherol concentrations and reduced plasma lipids in human subjects given an almond supplemented diet.
Additionally, flaxseed is a rich source of lignans, alpha-linolenic acid and soluble fiber mucilage. The effect of flaxseed was studied by Lucas et al. in ovariectomized Golden Syrian hamsters (an animal model with significantly elevated plasma lipids). Flaxseed consumption reduced the aortic fatty streak area and the incidence of lesions to levels similar to the sham group. Further studying the affects of flaxseed, Gonthier et al. studied the changes in milk fatty acid composition in dairy cows fed with flaxseed. It was concluded that feeding raw or heated flaxseed to dairy cows altered the blood and milk fatty acid composition and feeding extruded flaxseed relative to raw or micronized flaxseed had a negative effect on milk yield and milk composition. Ingram et al. studied the effects of flaxseed and flax oil in a rat renal ablation model. Rats fed with flaxseed or flaxseed oil had slowed decline in renal function, and a favorable effect on blood pressure and plasma lipids.
Defatted flaxseed meal and flaxseed consumption and their effects were studied in rats by Wiesenfeld et al. Flaxseed more than defatted flaxseed meal altered fatty acid profiles. Defatted flaxseed and a 40% flaxseed diet significantly reduced serum cholesterol. They also found a reduction of liver vitamin E in rats fed a diet consisting of 40% flaxseed.
Little is known about the effect of flaxseed type, brown versus golden. Scheideler et al. studied the effects of flaxseed variety, level, form and storage conditions on egg production and composition among hens. Supplementation of flaxseed significantly increased percentage white and decreased yolk compared to control but had no effects on egg cholesterol. Flaxseed additionally decreased feed consumption, weight gain, and egg whites. The level of linolenic acid (C18:3n-3) into eggs increased linearly as the level of dietary flaxseed increased.
Stuglin and Prasad studied the effects of flaxseed consumption on serum lipids, hemopoitic system and liver and kidney function in healthy human volunteers. Daily ingestion of 32.7 grams (“g”) of flaxseed administered over a four week period of time did not have a deleterious effect on the hemopoitic system, or on the renal or hepatic system. The level of serum triglyceride was elevated.
Lucas et al. also studied the effect of flaxseed on biomarkers of bone metabolism in postmenopausal women. They did not find a benefit in that regard but flaxseed consumption was shown to improve lipid profiles (lowering of total cholesterol and non HDL lipoprotein cholesterol by 6%.)
Bierenbaum et al. studied the effect of flaxseed containing bread and ground flaxseed in 15 hyperlipemic human subjects. Serum total and LDL cholesterol levels were reduced significantly, while HDL cholesterol did not change. Also, thrombin-stimulated platelet aggregation decreased with supplement.
With regards to nuts, multiple studies are available describing the effect of a walnut containing diet on humans. For example, Abbey et al., in 1994, reported significant reduction of total and LDL cholesterol in male volunteers taking diet with almonds or walnuts. In 2000, Zambon et al. reported that substituting walnuts for monounsaturated fat improves the serum lipid profile of hyhpercholesterolemic men and women and the diet was well tolerated. The effect of walnut consumption in combined hyperlipidemia was reported by Almario et al., in 2001. Walnut supplementation beneficially altered the lipid distribution of the lipoprotein subclasses. In 2002, Feldman reviewed the scientific evidence for a beneficial health relationship between walnuts and coronary heart disease and confirmed these findings. Similar results were reported by Iwamoto et al. with Japanese male and female subjects. They also reported that the most prominent change was the elevation of alpha-linolenic acid that might be responsible for the lowering of LDL. The effect of walnut consumption was studied in subjects with borderline high total cholesterol by Morgan et al., in 2002, and in subjects with type-2 diabetes by Tapsell et al., in 2004. Theses studies revealed similar results: high HDL and low LDL without any significant change in body weight or glucose levels as based on a hemoglobin Alc (“HgAlc”) test. Ros et al., in 2004, reported that an increased consumption of walnuts improved endothelial function in hypercholesterolemic subjects.
Poppy seeds have a distinct set of sterols as described by Johansson. The nutritional value of poppy seed oil relative to other oils was studied in rats by Beare-Rogers et al. and the noted effects were similar to olive oil. Not much is currently known about the effect of poppy seeds on lipid level in humans.
Sesame seed on the other hand has been shown, by Yamashita et al., to increase vitamin E concentration in rats. Additionally, in 2001 Cooney et al. reported that sesame seed consumption has beneficial effects on plasma tocophorol, the major vitamers of vitamin E. This effect was not seen with consumption of walnuts or soy oil.
Liapkov in 1978 studied the effect of sunflower seed supplemented feed to rats. Liapkov reported a diminished level of endogenously formed triglycerides and cholesterol from the liver into the blood and a changed lipid composition of lipoproteins of a very low density in the blood. Nutritive value of sunflower seeds in a broiler diet was studied by Selvaraj et al. in 2004. Sunflower seed supplementation of up to 20% did not affect weight gain. Preservation of alpha-tocopherol and subsequent delay in rancidity in sunflower oil by herbs and spices was studied by Beddows et al. Besides describing effects of many other herbs and spices, they reported a beneficial effect of cumin extract and negative effect of cardamom extract upon preservation of alpha-tocopherol and delaying of sunflower seed oil rancidity.
Cardamom is a commonly used flavoring seed especially in eastern cuisine. AI-Zuhair et al. reported anti-inflammatory and anti-spasmodic properties of cardamom in animal models. Cardamom extract could inhibit platelet aggregation and lipid peroxidation was reported by Suneetha and Krishnakantha.
A direct comparison of “cholesterol-lowering” foods (soy-protein, almonds, viscous fibers from oats, barley, psyllium and the vegetables okra and eggplant) with a statin (lovastatin) was reported by Jenkins et al. in 2005. Mixed results were noted: LDL concentration decreased in both diets, with or without statin, and the absolute difference was greater with statin.
Aside from natural products, many pharmacological agents, such as statins, are available for correction of certain lipid abnormalities. However, these agents may have significant side effects. For example, a widely used statin, atorvastatin (Lipitor), may cause myopathy, liver toxicity, pancreatitis, myalgia/arthralgias and many other untoward effects. Many individuals cannot or hesitate to take those medications because of their potential side effects. Many of them look for a “natural” way to manage their lipids.
As stated, statins are a class of drugs used to lower blood cholesterol. They work in the liver to block a substance needed to make cholesterol. They may also help the body reabsorb cholesterol that has accumulated in plaques on the artery walls. This helps prevent further blockage in the blood vessels. Long-term use of statins may reduce existing blockage in narrowed blood vessels. In some people, statins have reduced the risk of heart attack and stroke. However, like all medications, statins have potential side effects. The most common side effects include nausea, diarrhea, constipation, and muscle ache. In addition, two potentially serious side effects are:
1. Elevated liver enzymes. Occasionally, statin use causes an increase in liver enzymes. If the increase is only mild, a individual can continue to take the drug. However, if the increase is severe, a individual may need to stop taking it, which usually reverses the problem. Additionally, certain other cholesterol-lowering drugs, such as gemfibrozil (Lopid) and niacin, increase the risk of liver problems in people who take statins. Because liver problems may develop without symptoms, people who take statins should have their liver function tested periodically.
2. Statin myopathy. Statins may cause muscle pain and tenderness (statin myopathy). In severe cases, muscle cells can break down (rhabdomyolysis) and release a protein called myoglobin into the bloodstream. Myoglobin can impair kidney function and lead to kidney failure. Certain drugs when taken with statins can increase the risk of rhabdomyolysis. These include gemfibrozil, erythromycin (Erythrocin), antifungal medications, nefazodone (Serzone), cyclosporine and niacin.
Individuals are instructed to avoid taking statins with grapefruit juice, which alters the body's metabolism of these drugs. Also, doctors generally recommend that people take statins late in the day because the body makes most of its cholesterol at night. Thus, the use of statins is difficult and risky.
An alternative approach to the problem of high cholesterol levels has been the use of ancient, cultural remedies, for example red yeast rice which has been used by the Chinese for many centuries as a food preservative, food colorant and for medicinal purposes to improve circulation and alleviate indigestion. Recently, Chinese and American scientists have developed red yeast rice as a product to lower blood lipids, including cholesterol and triglycerides.
Scientists at Pharmanex and the UCLA Center for Human Nutrition analyzed the properties of Cholestin™. The composition by weight is starch (73%), protein (5.8%) moisture (3-6%), unsaturated fatty acids (1.5%), monacolins (0.4%), ash (3%), and trace amounts of calcium, iron, magnesium, and copper. There are no additives, preservatives, heavy metals, or toxic substances, such as citrinic acid.
In 1977, Professor Endo in Japan discovered a natural cholesterol-lowering substance that is produced by a strain of Monascus yeast. This substance inhibits HMG-CoA reductase, an enzyme that is important for the production of cholesterol in the body. Professor Endo named this substance moncacolin K. Since then, scientists have discovered a total of 8 monacolin-like substances that have cholesterol-lowering properties.
Monacolin K is lovastatin, the active ingredient in the popular statin drug, Mevacor™, which is used for lowering cholesterol. Lovastatin also is believed to be the main cholesterol-lowering ingredient in HypoCol™ and Cholestin™. The lovastatin in Mevacor™ is highly purified and concentrated, while the ingredients in Cholestin™ and HypoCol™ are not. Thus, they contain much lower concentrations of lovastatin than Mevacor™. For example, each 600-mg capsule of Cholestin™ contains less than 2.4 mg of lovastatin whereas tablets of Mevacor™ contain 10 mg or more of this ingredient.
Because none of the components are purified and concentrated, HypoCol™ and Cholestin™ contain a mixture of the 8 yeast-produced monacolins, unsaturated fatty acids, and certain anti-oxidants. Some scientists believe that these other monacolins, unsaturated fatty acids, and anti-oxidants may work together favorably with lovastatin to enhance its cholesterol-lowering effects, as well as its ability in lowering triglycerides and increasing HDL cholesterol. (HDL is considered the “good” form of cholesterol since high levels of HDL cholesterol protect against heart attacks). Further studies in animals and humans will be necessary to test these beliefs.
Chinese scientists conducted most of the animal and human studies on this issue, using either Zhitai or Xuezhikang. The results of some 17 studies involving approximately 900 Chinese subjects with modestly elevated cholesterol levels have been published. In 8 of these studies, there was a control group that received a placebo (a pill with no active ingredients) for comparison purposes. In 9 of the studies, there was no placebo control group. These studies consistently showed that Zhitai and Xuezhikang lower total cholesterol (by an average of 10-30%), lower LDL cholesterol (by an average of 10-20%), lower triglycerides (by an average of 15-25%), and increase HDL (by an average of 7-15%).
Based on the above discussion, diets comprised of cholesterol lowering foods have provided mixed results. Additionally, there is a need for safer agents that individuals could confidently take to correct lipid abnormalities without the risk of significant side effects. There is a need for an easy to obtain, easily digestible, tasty, natural alternative. The present invention addresses this need.